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Title: Emodin, as a mitochondrial uncoupler, induces strong decreases in adenosine triphosphate (ATP) levels and proliferation of B16F10 cells, owing to their poor glycolytic reserve
Authors: Sugiyama, Yuma
Shudo, Toshiyuki
Hosokawa, Sho
Watanabe, Aki
Nakano, Masaki
Kakizuka, Akira  kyouindb  KAKEN_id
Author's alias: 杉山, 悠真
首藤, 敏之
中野, 将希
垣塚, 彰
Keywords: adenosine triphosphate
glycolytic reserve
Issue Date: Aug-2019
Publisher: Wiley
Journal title: Genes to Cells
Volume: 24
Issue: 8
Start page: 569
End page: 584
Abstract: Many types of cancer cells show a characteristic increase in glycolysis, which is called the “Warburg effect.” By screening plant extracts, we identified one that decreases cellular adenosine triphosphate (ATP) levels and suppresses proliferation of malignant melanoma B16F10 cells, but not of noncancerous MEF cells. We showed that its active ingredient is emodin, which showed strong antiproliferative effects on B16F10 cells both in vitro and in vivo. Moreover, we also found that emodin can function as a mitochondrial uncoupler. Consistently, three known mitochondrial uncouplers also displayed potent antiproliferative effects and preferential cellular ATP reduction in B16F10 cells, but not in MEF cells. These uncouplers provoked comparable mitochondrial uncoupling in both cell types, but they manifested dramatically different cellular effects. Namely in MEF cells, these uncouplers induced three to fivefold increases in glycolysis from the basal state, and this compensatory activation appeared to be responsible for the maintenance of cellular ATP levels. In contrast, B16F10 cells treated with the uncouplers showed less than a twofold enhancement of glycolysis, which was not sufficient to compensate for the decrease of ATP production. Together, these results raise the possibility that uncouplers could be effective therapeutic agents specifically for cancer cells with prominent “Warburg effect.”
Rights: This is the peer reviewed version of the following article: [Yuma Sugiyama, Toshiyuki Shudo, Sho Hosokawa, Aki Watanabe, Masaki Nakano, Akira Kakizuka. Emodin, as a mitochondrial uncoupler, induces strong decreases in adenosine triphosphate (ATP) levels and proliferation of B16F10 cells, owing to their poor glycolytic reserve. Genes to Cells, 24(8), 569-584], which has been published in final form at This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
The full-text file will be made open to the public on 12 August 2020 in accordance with publisher's 'Terms and Conditions for Self-Archiving'.
This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。
DOI(Published Version): 10.1111/gtc.12712
PubMed ID: 31234244
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